The effect of nitric oxide and peroxynitrite on apoptosis in human polymorphonuclear leukocytes

Morgan G. Blaylock, Brian H. Cuthbertson, Helen F. Galley*, N. Ranald Ferguson, Nigel R. Webster

*Corresponding author for this work

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

In acute lung injury, neutrophil apoptosis may be important in regulating the inflammatory process by controlling neutrophil numbers and thus activity. Exogenous inhaled nitric oxide is now a widely used therapy in patients with acute lung injury, and its effects on apoptosis may be important. We investigated the effect of nitric oxide and peroxynitrite on apoptosis in lipopolysaccharide stimulated polymorphonucIear leukocytes as a model of nitric oxide-treated lung injury. Cells were incubated for up to 16 h with and without 1.7 μg/ml lipopolysaccharide and the nitric oxide donor GEA-3162 or the peroxynitrite donor SIN-1. Apoptosis was assessed using flow cytometry following annexin-V staining, after 4, 6, 8, and 16 h. Data were assessed using Kruskal-Wallis analysis of variance or Mann-Whitney U-test as appropriate. Annexin-V staining increased spontaneously over 16 h in untreated cells (p = .0002) and incubation with either 1000 μM SIN-1 or 10 μM GEA-3162 increased annexin staining at early time points in nonactivated cells. Apoptosis was attenuated when cells were exposed to lipopolysaccharide and both nitric oxide and peroxynitrite dose dependently inhibited this suppression at all time points and was most apparent at 16 h (p = .004 and .001, respectively). Exposure of activated neutrophils to exogenous nitric oxide 07 peroxynitrite has marked influences on apoptosis. This work has implications for the modulation of neutrophil function within the lung in patients with lung injury who receive inhaled nitric oxide therapy.

Original languageEnglish
Pages (from-to)748-752
Number of pages5
JournalFree Radical Biology and Medicine
Volume25
Issue number6
DOIs
Publication statusPublished - 1 Oct 1998

Keywords

  • Apoptosis
  • Culture
  • Free radical
  • Human
  • Neutrophil
  • Nitric oxide
  • Peroxynitrite
  • Superoxide

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